This represents a competitive renewal of a portion of NIDA contract N01DA38200, entitled "Evaluation of New Pharmacotherapies for Treatment of Opiate Abuse. The portion of N01DA-3-8200 being renewed herein is that which serves the NIDA Opioid Treatment Discovery Program, the goal of which is to discover potential new medications for improved treatment of opioid abuse and dependence. The NIDA Opioid Treatment Discovery Program currently is focused on three clinical needs: (1) medications effective in preventing relapse following the cessation of opioid use (e.g., following medically facilitated withdrawal); (2) adjunct medications for converting patients from opioid agonist therapy to opioid antagonist or non-opioid therapy; and (3) improved non-opioid medications for treating opioid withdrawal symptoms. In brief, the objectives of this contract are: (1) to determine the in vivo activity and opiate receptor selectivity of novel opioid compounds; (2) to determine the effects of compounds in opiate-dependent animals, primarily during opiate withdrawal; (3) to evaluate compounds for their potential suitability for clinical trials as relapse prevention agents; and (4) to identify and acquire standard compounds which merit the aforementioned types of evaluation. The anticipated end results of this contract are written reports detailing study findings. These preclinical findings will, to a great extent, determine the NIDA Medication Development Division's future clinical trials in the area of improved treatments for heroin dependence.